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Year 2 - MCD Cancer > Invasion > Flashcards

Invasion Flashcards

1
Q

Steps of tumour progression?

A
  1. Homeostasis
  2. Genetic alterations
  3. Hyper-proliferation
  4. De-differentiation
    • Disassembly of cell-to-cell contacts
    • Loss of cell polarity
  5. Invasion
    • Increased motility
    • Cleavage of ECM proteins
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2
Q

What are the 2 types of migration?

A

Individual cell migration

Collective cell migration

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3
Q

Types of Individual cell migration?

A

Amoeboid - e.g. lymphomas

Mesenchymal (single) - e.g. fibrosarcoma

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4
Q

Types of collective cell migration?

A

Mesenchymal (chains) - e.g. fibrosarcoma

Cluster/cohorts - e.g. epithelial cancers

Multicellular strands/sheets - e.g. epithelial cancers
• collective cell migration requires more coordination to metastasise and so still has some cell-to-cell junctions

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5
Q

Describe tumour cell metastasis

A

Mimics morphogenetic events

  • e.g. branching morphogenesis in the mammary glands
  • e.g. migration of 1o glial cells to repair a scratch wound
  • the cells STOP migrating when contact is made
  • conversely, tumour cells will have NO clear migration front & no sense of direction
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6
Q

EGF and genes?

A

Administration of EGF can UPREGULATE genes involved in:
• cytoskeleton regulation
• motility machinery

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7
Q

What stimuli can cause a cell to move?

A

Organogenesis & morphogenesis

Wounding

GF/Chemosttractants

De-differentiation (tumours)

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8
Q

What tells a cell where to go when it moves?

A

Polarity (directionality)

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9
Q

What tells a cell to stop moving when it begins to move?

A

Contact-inhibition motility

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10
Q

How can a cell move?

A

Specialised structures
• focal adhesion
• lamellae
• filopodium

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11
Q

How is cell movement regulated?

A

The cells attach to the ECM via. INTEGRINS

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12
Q

What structures does the cell use for motility and explain this

A

Filopodia
• finger-like projections rich in actin filaments
• a bundle of parallel filaments

Lamellipodia
• sheet-like protrusions rich in actin filaments
• branched & crosslinked filaments

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13
Q

Why is control needed in cell movement?

A

Needed for/to:

  • Coordinate happenings inside the cell itself
  • Regulate adhesion/release of cell-ECM
  • To respond to external influences (sensors & directionality)
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14
Q

How are the cell structures for motility used to allow for motility?

A

Contraction of Filopodia and Lamellipodia can break old adhesions
• allowing the cell to maintain a motion
• a signal to move could be a nutrient source and the filaments can rapidly disassemble and then reassemble at a new site to move the cell

Actin filaments have a polarity
• there is a plus and minus end on which different proteins can bind
• Depending on the proteins that bind, the actin filaments can carry out different functions

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15
Q

What are the 4 broad mechanism actin goes through to allow for motility?

A
  1. Nucleation
  2. Elongation
  3. Capping
  4. Severing
  5. Cross-linking & bundling
  6. Branching
  7. Gel-Sol Transition (by actin severing)
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16
Q

Explain the (1) stage of actin which allow for motility

A

Nucleation

Attachment of the actin to the cell inner membrane
• ARP proteins form a complex and bind to actin monomers to create a nucleated actin filament (ARPs bind to the minus end)
• This is the limiting step in actin dynamics (formation of trimers to initiate polymerisation)

17
Q

Explain the (2) stage of actin which allows for motility

A

Profilin
• facilitates actin monomer binding to the actin filament

Thymosin
• reduces actin monomer binding by sequestering the free monomers so they are not available to bind to the actin filament

18
Q

Explain the (3) stage of actin which allows for motility

A

Capping

Addition of a capping molecule (to + or – end) to limit elongation
• +-end caps – Cap Z, Gelsolin, Fragmin/Severin.
• minus-end caps – Tropomodulin, Arp complex.

19
Q

Explain the (4) stage of actin which allows for motility

A

Severing

Breaking up actin filaments:
• unsevered actin filaments grow/shrink slowly
• severed populations grow/shrink more rapidly
- proteins – gelsolin, ADF/cofilin, fragmin/severin

20
Q

Explain the (5) stage of actin which allows for motility

A

Crosslinking & Bundling

This produces differing arrangements of actin filaments.

Proteins involved include:
	alpha-actinin.
	Fimbrin.
	Filamin.
	Spectrin.
	Villin.
	Vinculin.
21
Q

Explain the (6) stage of actin which allows for motility

A

Branching

This protein enables branches of actin to come off at 70degree angles
• protein – Arp complex

22
Q

Explain the (7) stage of actin which allows for motility

A

Gel-sol transition by actin filament severing

Gels are rigid and have NOT been severed
• Sols are not rigid (i.e. can flow) and HAVE been severed.

23
Q

Signalling mechanisms that regulate the actin cytoskeleton?

A
  1. Ion-flux changes
    • i.e. intracellular calcium
  2. Phosphoinositide signalling
    • i.e. phospholipid binding
  3. Kinases/phosphatases
    • i.e. phosphorylation of cytoskeletal proteins
  4. Signalling cascades via small GTPases
24
Q

Explain how small GTPases help regulate the cytoskeleton via. the signalling pathways

A

Rho, Rac, Cdc42 sub-families belongs to the Ras super-family.
• Cdc42 –> Filopodia production
• Rac –> Lamellipodia production
• Rho –> stress fibre production

These proteins are activated by:
• receptor tyrosine kinase
• adhesion receptors
• signal transduction pathways

(onenote!!)

Year 2 - MCD Cancer (14 decks)

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